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Extracellular vesicle–matrix interactions

Nature Reviews Materials volume 8, pages 390–402 (2023)Cite this article

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Abstract

The extracellular matrix (ECM) harbours various signals to control cellular functions and the materiality of tissues. Most efforts to synthetically reconstitute the matrix by biomaterial design have focused on decoupling cell-secreted and polymer-based cues. Cells package molecules into nanoscale lipid-membrane-bound extracellular vesicles (EVs) and secrete them. Thus, EVs inherently interact with the meshwork of the ECM. In this Review, we discuss various aspects of EV–matrix interactions. Cells receive feedback from the ECM and leverage intracellular processes to control the biogenesis of EVs. Once secreted, various biomolecular and biophysical factors determine whether EVs are locally incorporated into the matrix or transported out of the matrix to be taken up by other cells or deposited into tissues at a distal location. These insights can be utilized to develop engineered biomaterials in which EV release, retention and production can be precisely controlled to elicit various biological and therapeutic outcomes.

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Fig. 1: Cell-secreted nanoscale mediators.
Fig. 2: Biogenesis mechanisms of EVs in the ECM.
Fig. 3: Biomolecular interactions between EVs and the ECM.
Fig. 4: Biophysical mechanisms of EV transport in the extracellular matrix.
Fig. 5: Biomaterial strategies to control EV release.
Fig. 6: Biomaterial strategies to promote EV retention.

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Acknowledgements

This work was supported by NIH Grants R01-GM141147 (J.-W.S.), R01-HL141255 (J.-W.S.) and T32-HL007829 (A.R.), National Science Foundation CAREER Grant 2143857 (J.-W.S.) and Hebrew University of Jerusalem and University of Illinois Joint Research and Innovation Seed Grant (J.-W.S.). The authors acknowledge S. Badylak and G. Hussey (University of Pittsburgh) for initial discussion of the topic.

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  1. These authors contributed equally: Koushik Debnath, Kevin Las Heras.

Authors and Affiliations

  1. Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Koushik Debnath, Kevin Las Heras, Ambar Rivera, Stephen Lenzini & Jae-Won Shin

  2. Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, USA

    Koushik Debnath, Kevin Las Heras, Ambar Rivera, Stephen Lenzini & Jae-Won Shin

  3. NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy (UPV/EHU), Vitoria-Gasteiz, Spain

    Kevin Las Heras

  4. Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain

    Kevin Las Heras

  5. Department of Chemical Engineering, University of Illinois at Chicago, Chicago, IL, USA

    Ambar Rivera

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Debnath, K., Las Heras, K., Rivera, A. et al. Extracellular vesicle–matrix interactions. Nat Rev Mater 8, 390–402 (2023). https://doi.org/10.1038/s41578-023-00551-3

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